Parameterization of a geometric flow implicit solvation model

Abstract

Implicit solvent models are popular for their high computational efficiency and simplicity over explicit solvent models and are extensively used for computing molecular solvation properties. The accuracy of implicit solvent models depends on the geometric description of the solute-solvent interface and the solvent dielectric profile that is defined near the surface of the solute molecule. Typically, it is assumed that the dielectric profile is spatially homogeneous in the bulk solvent medium and varies sharply across the solute-solvent interface. However, the specific form of this profile is often described by ad hoc geometric models rather than physical solute-solvent interactions. Hence, it is of significant interest to improve the accuracy of these implicit solvent models by more realistically defining the solute-solvent boundary within a continuum setting. Recently, a differential geometry-based geometric flow solvation model was developed, in which the polar and nonpolar free energies are coupled through a characteristic function that describes a smooth dielectric interface profile across the solvent-solute boundary in a thermodynamically self-consistent fashion. The main parameters of the model are the solute/solvent dielectric coefficients, solvent pressure on the solute, microscopic surface tension, solvent density, and molecular force-field parameters. In this work, we investigate how changes in the pressure, surface tension, solute dielectric coefficient, and choice of different force-field charge and radii parameters affect the prediction accuracy for hydration free energies of 17 small organic molecules based on the geometric flow solvation model. The results of our study provide insights on the parameterization, accuracy, and predictive power of this new implicit solvent model.

Figure 1

The minimum root-mean-squared error χ_min versus solute dielectric coefficient, ε_m obtained from the different force-field calculations: AM1-BCCv1/ZAP-9 (with or without vdw), AM1-BCCv1/Bondi (with or without vdw), OPLS-AA (without vdw), and OPLS-AA (with vdw).

Figure 2

Comparison of calculated and experimental hydration free energies for the 17 molecules, at the optimal values of pressure, surface tension and solute dielectric coefficient, obtained using AM1-BCCv1/ZAP-9, AM1-BCCv1/Bondi, and OPLS-AA.

Figure 3

Comparison of errors in the hydration free energies (ΔG_calc − ΔG_expt) of each molecule, obtained from the different force-field calculations at the optimal values of pressure, surface tension, and solute dielectric coefficient.